ADMIN CORE: Project Summary/Abstract The Administrative Core of the competing renewal of this Program Project Grant (PPG) entitled ?Frontotemporal Dementias: Genotypes and Phenotypes? is Core A. This PPG was launched 15 years ago at the University of Pennsylvania and in the renewal period it will seek to advance understanding of mechanisms underlying the onset and progression of hereditary and sporadic forms of frontotemporal degeneration (FTD). These diverse clinical disorders are characterized by genetic and neuropathological heterogeneity. For example, FTD with underlying frontotemporal lobar degeneration (FTLD) due to neuronal and glial tau pathology (FTLD-Tau) account for ~45% of patients, while TDP-43 inclusions (FTLD-TDP) account for ~50% of affected individuals, and ~5% of cases have FUS lesions (FTLD-FUS) as the underlying neuropathology. Further, FTLD-Tau disorders, including corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and Pick's disease (PiD), are linked to genetic and environmental risk factors, and FTLD-Tau progression as well as heterogeneity may be driven mechanistically by the differential cell-to-cell spread of different species or strains of pathological tau. The major focus of this PPG competing renewal is on elucidating mechanisms underlying the onset, progression and heterogeneity of CBD, PSP and PiD. As the administrative unit of this PPG, Core A continues to exercise fiscal and administrative oversight of the PPG, facilitates interactions among PPG investigators to accomplish the PPG research goals, coordinates and integrates activities of the Projects/Cores, and provides mechanisms to advise PPG Core and Project Leaders on their progress towards accomplishing the mission of this PPG. This is achieved using strategies that have been very successful in this PPG during the current funding cycle. Hence, Core A provides a clearly delineated and proven administrative structure to foster and facilitate efforts by PPG investigators to elucidate mechanisms of the onset/progression and pathobiology of hereditary and sporadic FTLD-Tau disorders, especially CBD, PSP and PiD.